A pilot study on local glucocorticoid metabolism in the context of age, sex and genotype in human bone

Introduction: Glucocorticoids play a key role in bone metabolism. Prolonged exposure to glucocorticoids is known to contribute to bone loss and osteoporosis. While systemic glucocorticoid levels have been well studied, little is known about local concentrations in bone and their potential role in disease mechanisms. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), encoded by HSD11B1, regulates local cortisol availability. The expression of 11β-HSD1 in osteoblasts has been shown to increase with age. Beyond age related changes in gene regulation, genetic polymorphisms of HSD11B1, such as the SNP rs11811440, have been associated with alterations in bone quality. This pilot study aimed to establish a method for quantifying endogenous glucocorticoid levels in human bone and to examine their correlation with systemic levels, age, sex, and genotypes. Methods : Peripheral blood and local bone marrow samples were collected from 49 patients undergoing primary hip arthroplasty or periacetabular osteotomy. Following organic solvent extraction, glucocorticoid concentrations were quantified using LC-MS/MS. Genotyping of the HSD11B1 gene was performed using the rhAmp SNP genotyping system. Results : Cortisone and cortisol were reliably quantified in bone for the first time. No correlation was observed between systemic and local cortisol or cortisone levels. The cortisol-to-cortisone ratios showed significant differences between systemic and local concentrations. No significant differences were observed across age, sex, or genotype. Discussion: This pilot study demonstrates the feasibility of quantifying endogenous glucocorticoids in human bone, providing a basis for investigating local cortisol regulation. The absence of correlation between systemic and local endogenous glucocorticoid levels along with significant differences in cortisol-to-cortisone ratios, suggests an independent regulatory mechanism within the bone. These findings highlight the potential relevance of local cortisol metabolism for bone homeostasis and point to several important directions for future research. Further studies should include larger sample sizes and employ multivariate analyses that account for age, sex, genotype, the surgical procedure, as well as inflammatory status, to validate and extend these preliminary observations.